Insulin resistance is a key feature of type 2 diabetes, and is characterized by decreased glucose disposal, increased hepatic glucose production, with a reduced ability of insulin to maintain normal glucose homeostasis. Whole-body glucose metabolism is regulated by a complex communication network between various tissues, including adipose tissue, liver, muscle, and brain. Glucose transporter-4 (GLUT4) is the principal insulin-stimulated glucose transporter expressed primarily in adipose tissue and skeletal muscle. Insulin stimulates glucose uptake by inducing GLUT4 translocation to the plasma membrane. GLUT4 trafficking from intracellular compartments to the plasma membrane is regulated by a number of small GTPases, including Rab5 and its family member Rab31.
p75NTR is a member of the Tumor Necrosis Factor (TNF) receptor superfamily that was originally identified as a receptor for neurotrophins p75NTR is expressed in the nervous system and in adult non-neuronal tissues, such as white adipose tissue (WAT), and muscle. p75NTR has surprisingly diverse cellular functions, including modulation of cell survival, apoptosis and differentiation, which underlie its in vivo biologic functions, including liver and muscle regeneration, extracellular matrix remodeling, sensory neuron development, hypoxia, and the angiogenic response.
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